Voluntary participation of hemiplegic patients is crucial for functional electrical stimulation therapy. A wearable functional electrical stimulation system has been proposed for real-time volitional hand motor function control using the electromyography bridge method. Through a series of novel design concepts, including the integration of a detecting circuit and an analog-to-digital converter, a miniaturized functional electrical stimulation circuit technique, a low-power super-regeneration chip for wireless receiving, and two wearable armbands, a prototype system has been established with reduced size, power, and overall cost. Based on wrist joint torque reproduction and classification experiments performed on six healthy subjects, the optimized surface electromyography thresholds and trained logistic regression classifier parameters were statistically chosen to establish wrist and hand motion control with high accuracy. Test results showed that wrist flexion/extension, hand grasp, and finger extension could be reproduced with high accuracy and low latency. This system can build a bridge of information transmission between healthy limbs and paralyzed limbs, effectively improve voluntary participation of hemiplegic patients, and elevate efficiency of rehabilitation training.

The NESS Handmaster (Ijzerman et al., 1996) and the FES system (Nathan, 1989) belong to the push-button controlled FES method (or switch-based FES). Both of these methods use on/off stimulation with pre-programmed sequences to help spinal cord injury patients recover hand grasp movements and other daily functions. Electromyography (EMG) has been used for on/off control in EMG-triggered FES (Cauraugh et al., 2005) or proportional EMG-controlled FES (Saxena et al., 1995; Thorsen et al., 2001; Hara et al., 2013) and capitalizes on the principle of intension-driven motion. Therapeutic effects were reduced by approximately half if FES was applied without voluntary recipient involvement (Barsi et al., 2008). Preliminary results (McGie et al., 2015) suggest that motor-evoked potential of brain computer interface-controlled FES (Pfurtscheller et al., 2003) and EMG-controlled FES can elicit greater neuroplastic changes than conventional therapy. However, EMG-controlled FES requires some residual movement of the affected arm or hand, so it is not applicable with severely disabled stroke survivors. Contralaterally controlled FES is a promising therapy designed to improve recovery of paretic limbs after stroke. Two case series pilot studies (Knutson et al., 2009, 2014) and an early-phase randomized controlled trial (Knutson et al., 2012) verified the efficiency of contralaterally controlled FES. However, it is important for the success of FES therapy to include the contralateral limb in volitional control of electrically induced contraction in the affected limb.

Based on the success of volitional control of FES, our group previously designed an FES system for restoring motor function in post-stroke hemiplegic patients (Huang et al., 2014). In that system, a frequency-modulation stimulation algorithm based on surface EMG (sEMG) and the support vector machine model were used. However, sEMG thresholds need to be carefully chosen and force reproduction performance has not yet been established. The system is also too difficult to wear and remove.

The specific objectives of this paper were: (1) to use statistical experiments and analyses to optimize the primary parameter “sEMG thresholds” of the frequency-modulation stimulation generation algorithm formerly proposed by our group and to verify the force reproduction performance; (2) to develop a low-complexity algorithm based on logistic regression for hand movement classification achieved by these sEMG thresholds; (3) to develop a wireless and wearable FES system using the EMG-bridge method for real-time volitional hand motor function control, and to assess the feasibility of this system in real-time control of four hand movements. This novel system is a wearable EMG-bridge system that is distributed via a contralateral sEMG-controlled FES system providing more convenience to use at home. The size, power, and overall cost have been significantly reduced compared with the previous prototype (Huang et al., 2014).

Low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) to the contralesional hemisphere and intensive occupational therapy (iOT) have been shown to contribute to a significant improvement in upper limb hemiparesis in patients with chronic stroke. However, the effect of the combined intervention program of LF-rTMS and iOT on cognitive function is unknown. We retrospectively investigated whether the combined treatment influence patient’s Trail-Making Test part B (TMT-B) performance, which is a group of easy and inexpensive neuropsychological tests that evaluate several cognitive functions. Twenty-five patients received 11 sessions of LF-rTMS to the contralesional hemisphere and 2 sessions of iOT per day over 15 successive days. Patients with right- and left-sided hemiparesis demonstrated significant improvements in upper limb motor function following the combined intervention program. Only patients with right-sided hemiparesis exhibited improved TMT-B performance following the combined intervention program, and there was a significant negative correlation between Fugl-Meyer Assessment scale total score change and TMT-B performance. The results indicate the possibility that LF-rTMS to the contralesional hemisphere combined with iOT improves the upper limb motor function and cognitive function of patients with right-sided hemiparesis. However, further studies are necessary to elucidate the mechanism of improved cognitive function.

Introduction
Upper limb hemiparesis is reported to be observed in 55–75% of post-stroke patients, and affects the patient’s activities of daily living and quality of life (Nichols-Larsen et al., 2005; Wolf et al., 2006). Duncan et al. (1992) reported that dramatic recovery of motor function was completed by 1month post-stroke, and that recovery often plateaued by 6 months. In recent years, repetitive transcranial magnetic stimulation (rTMS) has attracted attention as a treatment technique for the sequelae of stroke. It is a non-invasive, painless method to stimulate regions of the cerebral cortex, in which a figure-8 or a round coil converts electrical current into a rapidly variable magnetic field that is orthogonal to the current. Eddy currents generated by the changes of the magnetic field directly affect neurons (Barker, 1999). In addition, it has been known that different stimulation frequencies have different effects on the activities of the cerebral cortex, with high-frequency (> 5 Hz) stimulation facilitating local neuronal excitability and low-frequency (< 1 Hz) stimulation showing inhibitory effects (Lefaucheur, 2006; Butler and Wolf, 2007). Low-frequency rTMS (LF-rTMS) aims at increasing the excitability of the ipsilesional hemisphere by exerting its effects on the disrupted interhemispheric inhibition following stroke and thereby providing inhibitory stimulation to the contralesional hemisphere. Meta-analyses of rTMS in patients with stroke indicate that LF-rTMS is recommended for stroke patients in the chronic phase (> 6 months post-stroke), showing a strong possibility of a significant improvement of their upper limb function (Hsu et al., 2012; Le et al., 2014). In the past, our research group implemented a 15-day treatment protocol consisting of LF-rTMS and an intensive individualized rehabilitation program for patients with upper limb hemiparesis following stroke, and demonstrated a significant improvement of upper limb hemiparesis (Kakuda et al., 2011, 2012, 2016). Furthermore, we investigated the effects of our treatment protocol on brain activity and demonstrated a significant increase in the fMRI laterality index, indicating increased neuronal activity in the ipsilesional hemisphere (Yamada et al., 2013). Our single photon emission computed tomography (SPECT) study also demonstrated a significant decrease in perfusion in the middle frontal gyrus (Brodmann area; BA6), precentralgyrus (BA4), and post central gyrus (BA3) of the contralesional hemisphere, as well as an increased perfusion in the insula (BA13) and precentral gyrus (BA44) of the ipsilesional hemisphere (Hara et al., 2013). Thus, we demonstrated changes in brain activity between pre- and post-treatment that combined LF-rTMS and an intensive occupational therapy (iOT) program.

In recent studies, rTMS was used not only in treating upper limb hemiparesis after stroke, but also for other conditions, including neurological and psychiatric disorders, pain, and Parkinson’s disease (Lefaucheur et al., 2014). Furthermore, some studies conducted neuropsychological examinations at the time of rTMS to evaluate its effect on cognitive function (Nardone et al., 2014; Drumond Marra et al., 2015). One study reported an improvement in cognitive function following rTMS in patients with mild cognitive impairment (Nardone et al., 2014). Drumond Marra et al. (2015) reported an improved performance on the Rivermead Behavioral Memory Test following high-frequency rTMS (HF-rTMS) to the left dorsolateral prefrontal cortex (DLPFC).

Furthermore, the effects of rTMS on cognitive function in addition to motor disorders, aphasia, and affective disorders have been attracting attention (Lefaucheur et al., 2014; Nardone et al., 2014; Drumond Marra et al., 2015). One study reported an improvement in Trail-Making Test part B (TMT-B) performance by HF-rTMS, while another study reported a lack of significant improvement relative to a control group (Moser et al., 2002; Mittrach et al., 2010). However, few studies have investigated the effects of LF-rTMS on cognitive function. As described earlier, LF-rTMS exerts an inhibitory stimulation to the side of administration and is considered to affect the contralateral cerebral cortices via a modulation of interhemispheric inhibition. Therefore, LF-rTMS possibly affects a broader region than that affected by HF-rTMS. Meta-analyses of rTMS in patients with stroke indicate that LF-rTMS is recommended for stroke patients in the chronic phase (> 6 months post-stroke).

Although previous studies indicate a possibility of positive effects of rTMS on cognitive function; however, to the best of our knowledge, there has been no report describing the effect of a combined intervention program of LF-rTMS and intensive occupational therapy (iOT) on cognitive function in post-stroke patients. Therefore, the present study aimed to explore the therapeutic effect of the combined intervention program on patients with post-stroke upper limb hemiparesis.

Gait disorders drastically affect the quality of life of stroke survivors, making post-stroke rehabilitation an important research focus. Noninvasive brain stimulation has potential in facilitating neuroplasticity and improving post-stroke gait impairment. However, a large inter-individual variability in the response to noninvasive brain stimulation interventions has been increasingly recognized. We first review the neurophysiology of human gait and post-stroke neuroplasticity for gait recovery, and then discuss how noninvasive brain stimulation techniques could be utilized to enhance gait recovery. While post-stroke neuroplasticity for gait recovery is characterized by use-dependent plasticity, it evolves over time, is idiosyncratic, and may develop maladaptive elements. Furthermore, noninvasive brain stimulation has limited reach capability and is facilitative-only in nature. Therefore, we recommend that noninvasive brain stimulation be used adjunctively with rehabilitation training and other concurrent neuroplasticity facilitation techniques. Additionally, when noninvasive brain stimulation is applied for the rehabilitation of gait impairment in stroke survivors, stimulation montages should be customized according to the specific types of neuroplasticity found in each individual. This could be done using multiple mapping techniques.

Introduction

The American Heart Association estimates that approximately 795,000 individuals in the United States have a stroke each year (Go et al., 2014). A lack of mobility is the main obstacle for stroke survivors seeking to regain daily living independence and social integration. Thus, restoring impaired gait is one of the major goals of post-stroke rehabilitation. Recently, traditional rehabilitation techniques have been augmented by the use of a new methodology, noninvasive brain stimulation (NIBS), which facilitates neuroplasticity. To better understand the use of NIBS, this paper reviews literature regarding the neurophysiology of human gait, poststroke neuroplasticity in the motor control system underlying gait, and finally, approaches for using NIBS to enhance gait recovery.

Neurophysiology of Human Gait

Involvement of the cerebral cortices: In functional neuroimaging studies of human walking, the premotor cortex (PMC) and the supplementary motor cortex (SMC) are activated prior to step onset (Huppert et al., 2013). However, lesions in these two areas often lead to problems with gait initiation and the negotiation of narrow passages (Jahn et al., 2004), indicating their importance in the initiation and planning of walking. Furthermore, corticospinal inputs significantly facilitate muscular responses in the lower limbs, especially during the swing phase of the step cycle (Pijnappels et al., 1998). These observations suggest that cortical outputs play a critical role in the modulation of lower limb locomotion…

Hemiparesis is one of the most common consequences of stroke. Advanced rehabilitation techniques are essential for restoring motor function in hemiplegic patients. Functional electrical stimulation applied to the affected limb based on myoelectric signal from the unaffected limb is a promising therapy for hemiplegia. In this study, we developed a prototype system for evaluating this novel functional electrical stimulation-control strategy. Based on surface electromyography and a vector machine model, a self-administered, multi-movement, force-modulation functional electrical stimulation-prototype system for hemiplegia was implemented. This paper discusses the hardware design, the algorithm of the system, and key points of the self-oscillation-prone system. The experimental results demonstrate the feasibility of the prototype system for further clinical trials, which is being conducted to evaluate the efficacy of the proposed rehabilitation technique.

Virtual reality is a new technology that simulates a three-dimensional virtual world on a computer and enables the generation of visual, audio, and haptic feedback for the full immersion of users. Users can interact with and observe objects in three-dimensional visual space without limitation. At present, virtual reality training has been widely used in rehabilitation therapy for balance dysfunction. This paper summarizes related articles and other articles suggesting that virtual reality training can improve balance dysfunction in patients after neurological diseases. When patients perform virtual reality training, the prefrontal, parietal cortical areas and other motor cortical networks are activated. These activations may be involved in the reconstruction of neurons in the cerebral cortex. Growing evidence from clinical studies reveals that virtual reality training improves the neurological function of patients with spinal cord injury, cerebral palsy and other neurological impairments. These findings suggest that virtual reality training can activate the cerebral cortex and improve the spatial orientation capacity of patients, thus facilitating the cortex to control balance and increase motion function.

Mental practice is a new rehabilitation method that refers to the mental rehearsal of motor imagery content with the goal of improving motor performance. However, the relationship between activated regions and motor recovery after mental practice training is not well understood. In this study, 15 patients who suffered a first-ever subcortical stroke with neurological deficits affecting the right hand, but no significant cognitive impairment were recruited. 10 patients underwent mental practice combined with physical practice training, and 5 patients only underwent physical practice training. We observed brain activation regions after 4 weeks of training, and explored the correlation of activation changes with functional recovery of the affected hands. The results showed that, after 4 weeks of mental practice combined with physical training, the Fugl-Meyer assessment score for the affected right hand was significantly increased than that after 4 weeks of practice training alone. Functional MRI showed enhanced activation in the left primary somatosensory cortex, attenuated activation intensity in the right primary motor cortex, and enhanced right cerebellar activation observed during the motor imagery task using the affected right hand after mental practice training. The changes in brain cortical activity were related to functional recovery of the hand. Experimental findings indicate that cortical and cerebellar functional reorganization following mental practice contributed to the improvement of hand function.